9-Deoxy-9-methylene-PGF2 cycloamides

ABSTRACT

The present invention relates to novel 9-deoxy-9-methylene-PGF 2  cycloamides. These compounds are useful pharmacological agents, and are useful for the same purposes as the corresponding 9-deoxy-9-methylene-PGF-type acids.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of Ser. No. 786,250, filed Apr. 11, 1977, now U.S. Pat. No. 4,098,805.

The present invention relates to novel 9-deoxy-9-methylene-PGF₂ cycloamides, the essential material constituting a disclosure of which is incorporated here by reference from Ser. No. 786,250. 

I claim:
 1. A prostaglandin analog of the formula ##STR1## wherein Y₁ is trans--CH═CH--, --C.tbd.C-, or --CH₂ CH₂ --;wherein M₁ is ##STR2## wherein R₅ is hydrogen or methyl;Wherein L₂ is ##STR3## or a mixture of ##STR4## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro;Wherein Z₃ is(1) cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --, (2) cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --, or (3) cis--CH₂ --CH═CH-(CH₂)_(g) --CH₂ --,wherein G is one, 2, or 3;Wherein R₇ is ##STR5## WHEREIN M IS ONE TO 5, INCLUSIVE, H IS ZERO OR ONE, T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive, and s is zero, one, 2, or 3, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl, with the further proviso that R₇ is ##STR6## WHEREIN T and s are as defined above, only when R₃ and R₄ are hydrogen or methyl, being the same or different; andWherein L₆ is cycloamino of the formula ##STR7## ##STR8## wherein R₂₁ and R₂₂ are hydrogen, alkyl of one to 12 carbon atoms, inclusive; aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, 2, or 3 chloro or alkyl of one to 3 carbon atoms, inclusive, or phenyl substituted with hydroxycarbonyl or alkoxycarbonyl of one to 4 carbon atoms, inclusive.
 2. A prostaglandin analog according to claim 1, wherein Y₁ is --C.tbd.C--.
 3. 9-Deoxy-9-methylene-13,14-didehydro-PGF₂, pyrrolidylamide, a prostaglandin analog according to claim
 2. 4. 9-Deoxy-9-methylene-13,14-didehydro-PGF₂, piperidylamide, a prostaglandin analog according to claim
 2. 5. 9-Deoxy-9-methylene-13,14-didehydro-PGF₂, morpholinylamide, a prostaglandin analog according to claim
 2. 6. 9-Deoxy-9-methylene-13,14-didehydro-PGF₂, hexamethyliminoamide, a prostaglandin analog according to claim
 2. 7. 9-Deoxy-9-methylene-13,14-didehydro-PGF₂, piperazinylamide, a prostaglandin analog according to claim
 2. 8. 9-Deoxy-9-methylene-13,14-didehydro-PGF₂, 3,4-didehydropyrrolidylamide, a prostaglandin analog according to claim
 2. 9. 9-Deoxy-9-methylene-13,14-didehydro-PGF₂, 3,4-didehydropiperidylamide, a prostaglandin analog according to claim
 2. 10. A prostaglandin analog according to claim 1, wherein Y₁ is -CH₂ CH₂ -.
 11. 9-Deoxy-9-methylene-13,14-dihydro-PGF₂, pyrrolidylamide, a prostaglandin analog according to claim
 10. 12. 9-Deoxy-9-methylene-13,14-dihydro-PGF₂, piperidylamide, a prostaglandin analog according to claim
 10. 13. 9-Deoxy-9-methylene-13,14-dihydro-PGF₂, morpholinylamide, a prostaglandin analog according to claim
 10. 14. 9-Deoxy-9-methylene-13,14-dihydro-PGF₂, hexamethyliminoamide, a prostaglandin analog according to claim
 10. 15. 9-Deoxy-9-methylene-13,14-dihydro-PGF₂, piperazinylamide, a prostaglandin analog according to claim
 10. 16. 9-Deoxy-9-methylene-13,14-dihydro-PGF₂, 3,4-didehydropyrrolidylamide, a prostaglandin analog according to claim
 10. 17. 9-Deoxy-9-methylene-13,14-dihydro-PGF₂, 3,4-didehydropiperidylamide, a prostaglandin analog according to claim
 10. 18. A prostaglandin analog according to claim 1, wherein Y₁ is trans--CH═CH--.
 19. A prostaglandin analog according to claim 18, wherein M₁ is ##STR9##
 20. 15-epi-9-Deoxy-9-methylene-PGF₂, pyrrolidylamide, a prostaglandin analog according to claim
 19. 21. 15-epi-9-Deoxy-9-methylene-PGF₂, piperidylamide, a prostaglandin analog according to claim
 19. 22. 15-epi-9-Deoxy-9-methylene-PGF₂, morphonylamide, a prostaglandin analog according to claim
 19. 23. 15-epi-9-Deoxy-9-methylene-PGF₂, hexamethyliminoamide, a prostaglandin analog according to claim
 19. 24. 15-epi-9-Deoxy-9-methylene-PGF₂, piperazinylamide, a prostaglandin analog according to claim
 19. 25. 15-epi-9-Deoxy-9-methylene-PGF₂, 3,4-didehydropyrrolidylamide, a prostaglandin analog according to claim
 19. 26. 15-epi-9-Deoxy-9-methylene-PGF₂, 3,4-didehydropiperidylamide, a prostaglandin analog according to claim
 19. 27. A prostaglandin analog according to claim 18, wherein M₁ is ##STR10##
 28. A prostaglandin analog according to claim 27, wherein Z₃ is cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ -.
 29. A prostaglandin analog according to claim 28, wherein R₇ is ##STR11##
 30. 9-Deoxy-9-methylene-17-phenyl-18,19,20-trinor-PGF₂, pyrrolidylamide, a prostaglandin analog according to claim
 29. 31. 9-Deoxy-9-methylene-17-phenyl-18,19,20-trinor-PGF₂, piperidylamide, a prostaglandin analog according to claim
 29. 32. 9-Deoxy-9-methylene-17-phenyl-18,19,20-trinor-PGF₂, morpholinylamide, a prostaglandin analog according to claim
 29. 33. 9-Deoxy-9-methylene-17-phenyl-18,19,20-trinor-PGF₂, hexamethyliminoamide, a prostaglandin analog according to claim
 29. 34. 9-Deoxy-9-methylene-17-phenyl-18,19,20-trinor-PGF₂, piperazinylamide, a prostaglandin analog according to claim
 29. 35. 9-Deoxy-9-methylene-17-phenyl-18,19,20-trinor-PGF₂, 3,4-didehydropyrrolidylamide, a prostaglandin analog according to claim
 29. 36. 9-Deoxy-9-methylene-17-phenyl-18,19,20-trinor-PGF₂, 3,4-didehydropiperidylamide, a prostaglandin analog according to claim
 29. 37. A prostaglandin analog according to claim 28, wherein R₇ is ##STR12##
 38. 9-Deoxy-9-methylene-16-phenoxy-17,18,19,20-tetranor-PGF₁, pyrrolidylamide, a prostaglandin analog according to claim
 37. 39. 9-Deoxy-9-methylene-16-phenoxy-17,18,19,20-tetranor-PGF₁, piperidylamide, a prostaglandin analog according to claim
 37. 40. 9-Deoxy-9-methylene-16-phenoxy-17,18,19,20-tetranor-PGF₁, morpholinylamide, a prostaglandin analog according to claim
 37. 41. 9-Deoxy-9-methylene-16-phenoxy-17,18,19,20-tetranor-PGF₁, hexamethyliminoamide, a prostaglandin analog according to claim
 37. 42. 9-Deoxy-9-methylene-16-phenoxy-17,18,19,20-tetranor-PGF₁, piperazinylamide, a prostaglandin analog according to claim
 37. 43. 9-Deoxy-9-methylene-16-phenoxy-17,18,19,20-tetranor-PGF₁, 3,4-didehydropyrrolidylamide, a prostaglandin analog according to claim
 37. 44. 9-Deoxy-9-methylene-16-phenoxy-17,18,19,20-tetranor-PGF₁, 3,4-didehydropiperidylamide, a prostaglandin analog according to claim
 37. 45. A prostaglandin analog according to claim 28, wherein R₇ is -(CH₂)_(m) -CH₃.
 46. A prostaglandin analog according to claim 45, wherein m is
 3. 47. A prostaglandin analog according to claim 46, wherein g is
 3. 48. 2a,2b-Dihomo-9-deoxy-9-methylene-15-methyl-PGF₂, pyrrolidylamide, a prostaglandin analog according to claim
 47. 49. 2a,2b-Dihomo-9-deoxy-9-methylene-15-methyl-PGF₂, piperidylamide, a prostaglandin analog according to claim
 47. 50. 2a,2b-Dihomo-9-deoxy-9-methylene-15-methyl-PGF₂, morpholinylamide, a prostaglandin analog according to claim
 47. 51. 2a,2b-Dihomo-9-deoxy-9-methylene-15-methyl-PGF₂, hexamethyliminoamide, a prostaglandin analog according to claim
 47. 52. 2a,2b-Dihomo-9-deoxy-9-methylene-15-methyl-PGF₂, piperazinylamide, a prostaglandin analog according to claim
 47. 53. 2a,2b-Dihomo-9-deoxy-9-methylene-15-methyl-PGF₂, 3,4-didehydropyrrolidylamide, a prostaglandin analog according to claim
 47. 54. 2a,2b-Dihomo-9-deoxy-9-methylene-15-methyl-PGF₂, 3,4-didehydropiperidylamide, a prostaglandin analog according to claim
 47. 55. A prostaglandin analog according to claim 46, wherein g is one.
 56. A prostaglandin analog according to claim 55, wherein at least one of R₃ and R₄ is methyl.
 57. 9-Deoxy-9-methylene-16,16-dimethyl-PGF₂, pyrrolidylamide, a prostaglandin analog according to claim
 56. 58. 9-Deoxy-9-methylene-16,16-dimethyl-PGF₂, piperidylamide, a prostaglandin analog according to claim
 56. 59. 9-Deoxy-9-methylene-16,16-dimethyl-PGF₂, morpholinylamide, a prostaglandin analog according to claim
 56. 60. 9-Deoxy-9-methylene- 16,16-dimethyl-PGF₂, hexamethyliminoamide, a prostaglandin analog according to claim
 56. 61. 9-Deoxy-9-methylene-16,16-dimethyl-PGF₂, piperazinylamide, a prostaglandin analog according to claim
 56. 62. 9-Deoxy-9-methylene-16,16-dimethyl-PGF₂, 3,4-didehydropyrrolidylamide, a prostaglandin analog according to claim
 56. 63. 9-Deoxy-9-methylene-16,16-dimethyl-PGF₂, 3,4-didehydropiperadylamide, a prostaglandin analog according to claim
 56. 64. A prostaglandin analog according to claim 55, wherein at least one of R₃ and R₄ is fluoro.
 65. 9-Deoxy-9-methylene-16,16-difluoro-PGF₂, pyrrolidylamide, a prostaglandin analog according to claim
 64. 66. 9-Deoxy-9-methylene-16,16-difluoro-PGF₂, piperidylamide, a prostaglandin analog according to claim
 64. 67. 9-Deoxy-9-methylene-16,16-difluoro-PGF₂, morpholinylamide, a prostaglandin analog according to claim
 64. 68. 9-Deoxy-9-methylene-16,16-difluoro-PGF₂, hexamethyliminoamide, a prostaglandin analog according to claim
 64. 69. 9-Deoxy-9-methylene-16,16-difluoro-PGF₂, piperazinylamide, a prostaglandin analog according to claim
 64. 70. 9-Deoxy-9-methylene-16,16-difluoro-PGF₂, 3,4-didehydropyrrolidylamide, a prostaglandin analog according to claim
 64. 71. 9-Deoxy-9-methylene-16,16-difluoro-PGF₂, 3,4-didehydropiperadylamide, a prostaglandin analog according to claim
 64. 72. A prostaglandin analog according to claim 55, wherein R₃ and R₄ are both hydrogen.
 73. A prostaglandin analog according to claim 72, wherein R₅ is methyl.
 74. 9-Deoxy-9-methylene-15-methyl-PGF₂, pyrrolidylamide, a prostaglandin analog according to claim
 73. 75. 9-Deoxy-9-methylene-15-methyl-PGF₂, piperidylamide, a prostaglandin analog according to claim
 73. 76. 9-Deoxy-9-methylene-15-methyl-PGF₂, morpholinylamide, a prostaglandin analog according to claim
 73. 77. 9-Deoxy-9-methylene-15-methyl-PGF₂, hexamethyliminoamide, a prostaglandin analog according to claim
 73. 78. 9-Deoxy-9-methylene-15-methyl-PGF₂, piperazinylamide, a prostaglandin analog according to claim
 73. 79. 9-Deoxy-9-methylene-15-methyl-PGF₂, 3,4-didehydropyrrolidylamide, a prostaglandin analog according to claim
 73. 80. 9-Deoxy-9-methylene-15-methyl-PGF₂, 3,4-didehydropiperadylamide, a prostaglandin analog according to claim
 73. 81. A prostaglandin analog according to claim 72, wherein R₅ is hydrogen.
 82. 9-Deoxy-9-methylene-PGF₂, pyrrolidylamide, a prostaglandin analog according to claim
 81. 83. 9-Deoxy-9-methylene-PGF₂, piperidylamide, a prostaglandin analog according to claim
 81. 84. 9-Deoxy-9-methylene-PGF₂, morpholinylamide, a prostaglandin analog according to claim
 81. 85. 9-Deoxy-9-methylene-PGF₂, hexamethyliminoamide, a prostaglandin analog according to claim
 81. 86. 9-Deoxy-9-methylene-PGF₂, piperazinylamide, a prostaglandin analog according to claim
 81. 87. 9-Deoxy-9-methylene-PGF₂, 3,4-didehydropyrrolidylamide, a prostaglandin analog according to claim
 81. 88. 9-Deoxy-9-methylene-PGF₂, 3,4-didehydropiperazinylamide, a prostaglandin analog according to claim
 81. 